The objectives of this research proposal are: 1) to determine whether changes in medullary ECF pH play a role in stimulating breathing during acclimatization to chronic hypoxia; 2) to determine whether changes in medullary ECF pH play a role in stimulating breathing during acute metabolic acidosis in peripheral chemoreceptor-denervated animals; 3) to test whether peripheral chemoreceptors are necessary for ventilatory acclimatization to hypoxia. To this end we will perform the following experiments: 1) simultaneous measurement of medullary ECF pH, cisternal CSF pH and integrated phrenic nerve activity in anesthetized, peripheral chemodenervated, paralyzed cats during isocapnic-hypoxia; 2) simultaneous measurement of medullary ECF pH, cisternal CSF pH and ventilation in anesthetized, peripheral chemoreceptor-intact cats during hypoxia; 3) simultaneous measurement of medullary ECF pH, cisternal CSF pH and ventilation in anesthetized, peripheral chemoreceptor-denervated cats during hypoxia; 4) simultaneous measurement of medullary ECF pH, cisternal CSF pH and ventilation in anesthetized, peripheral chemoreceptor-denervated cats during acute metabolic acidosis induced by i.v. infusion of 0.2 N HCl.